The long-term objective of this research is to make pulsatile heart replacement systems available to smaller adult patients. This is a non- trivial matter, because reduction in the size of a pulsatile blood pump affects (1) the fluid dynamics of the pump, (2) the energetics of the pump and actuator, and (3) the stresses experienced by the blood contacting materials. Thus, we consider studies such as those described here to be critical to the availability of artificial hearts and pulsatile ventricular assist devices for the full spectrum of adult patients. We propose to study the underlying principles of pump size reduction through three specific aims: First, we will compare in vitro measurements of the flow field with in vivo measures of thrombogenesis and hemolysis. Specifically, we will use Laser Doppler Anemometry and Particle Image Velocimetry to measure fluid velocity and shear rate, with a high degree of spatial and temporal resolution, in pump chambers designed according to various scaling parameters. Classical dimensionless analysis will serve as guidance in scaling to achieve fluid dynamic similitude, and to generalize these measurements for predictive purposes. The significance of these findings will be assessed through in vivo studies in calves using completely implanted total artificial hearts, using the same pump chambers under similar fluid dynamic conditions. Thrombogenesis will be assessed through hematology studies and explant analysis. Platelet and fibrin adhesion will be quantified using histological examination and epi-fluorescence microscopy, using fluorescently labeled platelets and fibrinogen. Novel rapid manufacturing methods will be used to fabricate the variety of pumping chambers required for these experiments. Secondly, we will develop relationships governing energetic performance of the system, utilizing a computer simulation of the energy converter, blood pump, circulation, controller, and energy transmission system. We will thereby optimize the major subsystems to minimize power consumption. Results will be validated on a mock circulatory loop. Thirdly, we will study the effects of reduced pump chamber size and pump shape parameters on biomaterial stresses using finite element analysis. Predicted strains will be validated using staticly pressurized pump chambers. We expect that this research will be broadly applicable to pulsatile blood pump design, especially by improving our understanding of the relationships between fluid dynamics and thrombogenesis in a complex, time-varying flow field. This work requires a multi-disciplinary effort in surgery, engineering, fluid mechanics, and hematology, with the means to efficiently manufacture blood pump systems and carry out the necessary in vitro and in vivo studies.